Lower Cellular Immune Responses Research Articles

Impairment of lymphocyte function following yttrium-90 DOTATOC therapy.

The radiolabeled somatostatin analogue, yttrium-90 DOTA-D-Phe(1)-Tyr(3)-octreotide (DOTATOC), is currently applied to treat advanced somatostatin receptor-positive tumors, e.g., neuroendocrine tumors of the pancreas, lung or gut. However, effects of this treatment on antimicrobial immune responses are not yet defined. In 20 patients treated with DOTATOC, cellular in vitro immune function was determined. Their antimicrobial lymphocyte responses were assessed by lymphocyte transformation test and enzyme-linked immunospot-measuring lymphocyte proliferation and on a single cell level production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10)-prior to therapy, at day 1, day 7 and day 90 post-therapy. Proliferative lymphocyte responses and interferon-γ production after in vitro stimulation with microbial antigens were non-significantly suppressed at day 1 and significantly (p<0.05) at day 7 versus pre-therapy. In vitro immune responses did not fully recover until day 90. In contrast, at day 1 interleukin-10 production was significantly (p<0.05) increased. Taken together, we observed a decrease in pro-inflammatory immune responses after DOTATOC therapy. Patients with versus without bone metastases displayed significantly (p<0.05) lower cellular immune responses toward several microbial antigens. Progressive disease and higher tumor burden could also be defined as factors associated with impaired immune function. Spearman correlation analysis indicated that cellular in vitro immunity was positively correlated with kidney function; better kidney function led to stronger immune responses. In conclusion, DOTATOC therapy caused a decrease in in vitro immune responses against microorganisms. The clinical impact needs to be evaluated in further studies.

Lower cellular immune responses to influenza A (H3N2) in the elderly

Influenza epidemic is an important cause of severe illness in the elderly. Age-dependent morbidity of influenza in the elderly is associated with weakened immunity. The baseline age-related memory T cell activity in Chinese persons who are exposed to influenza virus through natural infection, are associated with the protective response to the virus after vaccination, thus providing important pre-vaccination information. A cohort from the general population was established at the end of an influenza season in an area where influenza occurs regularly, and followed for 24 weeks. The subjects had no vaccination history for 5 years. Memory T cell responses were evaluated using a set of peptides spanning the influenza A (H3N2) entire proteome in a gamma interferon (IFN-gamma)-enzyme-linked immunospot (ELISPOT) assay, prior to the next influenza season. Changes of hemagglutination inhibition (HI) antibody titers were also evaluated. IFN-gamma(+) T cell responses against influenza peptides were significantly lower in subjects of 60 years and older. Although the age-related decline of cellular immune response was clear, no significant association of antibody titers with age was found. The pre-vaccination baseline of memory IFN-gamma(+) T cell immunity state in elderly Chinese was significantly lower than in people younger than 60 years. Measurement of the ex vivo cellular immune responses to influenza should be incorporated into the evaluation of protective immunity in elderly persons.

Clinical features of cutaneous and disseminated cutaneous leishmaniasis caused byLeishmania (Viannia) braziliensisin Paraty, Rio de Janeiro

American tegumentary leishmaniasis (ATL) caused by Leishmania (Viannia) braziliensis is endemic in Rio de Janeiro State (RJ), where the disease shows epidemiologic and clinical characteristics distinct from those of ATL in other Brazilian regions. Paraty is the second most important endemic area in RJ; however, reports on leishmaniasis in this region refer to the occurrence of the disease without describing its characteristics. The clinical features of 71 cases of ATL reported between 1991 and 1997 in Paraty are presented. Thirty patients were re-evaluated 10 years later. Males and females were affected in similar proportions, and the disease was more prevalent in patients aged between 10 and 49 years (63.4%). Cutaneous leishmaniasis was the most prevalent clinical form observed. Unique lesions were present in 69% of cases, 91.6% of which displayed an ulcerated aspect. Although mucosal leishmaniasis was not observed, severe clinical manifestations, such as disseminated cutaneous lesions caused by L. braziliensis, were diagnosed in two patients. These patients presented skin lesions with different clinical aspects spread throughout the body, as well as low cellular immune responses. Montenegro skin test (92% positivity) and serology (8% IgM and 56% IgG anti-Leishmania positive results) were the most utilized tests for supporting the diagnosis of leishmaniasis. Parasites, detected in 27 of the 33 cases analyzed, were characterized as L. braziliensis. ATL in Paraty shares the clinical and laboratory characteristics reported for ATL in other regions of RJ, probably because of the similar epidemiologic context related to the Atlantic rainforest region.

Coreceptor Switch in R5-Tropic Simian/Human Immunodeficiency Virus-Infected Macaques

The basis for the switch from CCR5 to CXCR4 coreceptor usage seen in approximately 50% of human immunodeficiency virus type 1 (HIV-1) subtype B-infected individuals as disease advances is not well understood. Among the reasons proposed are target cell limitation and better immune recognition of the CXCR4 (X4)-tropic compared to the CCR5 (R5)-tropic virus. We document here X4 virus emergence in a rhesus macaque (RM) infected with R5-tropic simian/human immunodeficiency virus, demonstrating that coreceptor switch can happen in a nonhuman primate model of HIV/AIDS. The switch to CXCR4 usage in RM requires envelope sequence changes in the V3 loop that are similar to those found in humans, suggesting that the R5-to-X4 evolution pathways in the two hosts overlap. Interestingly, compared to the inoculating R5 virus, the emerging CXCR4-using virus is highly neutralization sensitive. This finding, coupled with the observation of X4 evolution and appearance in an animal with undetectable circulating virus-specific antibody and low cellular immune responses, lends further support to an inhibitory role of antiviral immunity in HIV-1 coreceptor switch.

The Effect of Edrecolomab (Mo17-1A) or Fluorouracil-Based Chemotherapy on Specific Immune Parameters in Patients with Colorectal Cancer

Objectives: We investigated the immune profile of patients with resected Dukes’ stage C colorectal cancer (CRC), receiving adjuvant therapy with edrecolomab (Mo17-1A) or first-line 5-fluorouracil (5-FU)-based chemotherapy. Patients and Methods: Patients received either 5 doses of Mo17-1A over 13 weeks, or 5-FU/leucovorin, or 5-FU/levamisole over 6 and 12 months, respectively. Peripheral blood was collected postoperatively and 4 months after therapy initiation. Peripheral blood mononuclear cells were tested in the autologous mixed lymphocyte reaction (AMLR), for natural killer (NK) and lymphokine-activated killer (LAK) cell activity. Serum cytokines were quantified by ELISA. Results: Fifty-two patients entered the study. Postoperatively, they exhibited decreased levels of interleukin (IL)-2, interferon-γ, IL-12, granulocyte-macrophage colony-stimulating factor and IL-15, low cellular immune responses (AMLR, NK- and LAK-cytotoxicity) and increased levels of IL-1β, tumor necrosis factor-α, IL-6, IL-10 and prostaglandin E₂. After four months of therapy, patients receiving edrecolomab demonstrated enhanced AMLR, NK, LAK activity, increased serum levels of cytokines regulating such responses and reduced levels of acute-phase cytokines and immune suppressors, compared to patients treated with conventional chemotherapy. Conclusions: Postoperative adjuvant therapy with edrecolomab restores the in vivo deficient immune responses of patients with resected Dukes’ C CRC despite its clinical ineffectiveness in recent randomized adjuvant trials. These results suggest that further immunological studies with the combination of edrecolomab and chemotherapy are required.

Differences in immune responses to a low-molecular compound in three guinea-pig strains.

The present experiments were undertaken to clarify the differences in humoral and cellular immune responses to a low-molecular compound, sodium 2,4,6-trinitrobenznnesul fonate dihydrate (TNBS) in guinea-pig strains. Guinea pigs of three different strains, Hartley, Strain 2 and Strain 13, were immunized subcutaneously with TNBS (3 mg/body) 2 or 3 times a week, 9 times in total. Humoral immune responses to TNBS were assessed by passive cutaneous anaphylaxis (PCA) and Arthus reaction, and cellular immune response was assessed by delayed-type hypersensitivity (DTH). Hartley guinea pigs showed high humoral immune responses to TNBS, whereas Strain 2 and 13 guinea pigs showed low responses. Strain 2 guinea pigs displayed high cellular immune response to TNBS, and Strain 13 displayed low cellular immune responses. These results suggest that the pattern of humoral immune response to TNBS does not correlate with that of the cellular immune responses to TNBS for Strain 2 and Hartley guinea pigs.