Impairment of alternate pathway (CD2) of T cell activation in leprosy

Recent studies in basic immunology have been directed towards the understanding of the mechanism of T cell activation. T cells can be activated to proliferate via the classical pathway through the antigen receptor (CD3-Ti) or via the alternate pathway through the CD2 receptor. Since immunologic unresponsiveness in lepromatous leprosy is considered to be due to the inability of T cells to proliferate upon stimulation, we have been interested in the nature of these receptors and the activation pathways in lymphocytes of leprosy patients. In the present investigation we demonstrate: (i) CD2 receptor (Ereceptor) is downregulated in bacterial index positive lepromatous leprosy patients. (ii) The alternate pathway of T cell activation is impaired in lepromatous patients as revealed by the inability of their lymphocytes to proliferate in response to a pair of mitogenic anti-CD2 monoclonals. (iii) The addition of recombinant interleukin 2 in vitro restores the ability of lymphocytes from lepromatous patients to proliferate in response to anti-CD2 antibodies. (iv) Interestingly, CD2 modulation and the associated functional impairment could be brought about in peripheral blood lymphocytes from normal subjects by prior treatment with Mycobacterium leprae in vitro. This approach would be useful in understanding the molecular events leading to the defective T cell functions in leprosy

Immunological status of patients of Eales' disease

To test the hypothesis that altered immune reactivity to an extraneous agent might lead to primary retinal perivasculitis, a study was undertaken to determine the serum immunoglobulin levels, T lymphocyte subsets, antibody responses to BCG and 'S' antigen, and lymphoproliferative response to mitogens. No difference was observed in these parameters between patients and controls. Both Mantoux positive and negative conditions existed in patients with Eales' disease. Mantoux positive patients showed a higher level of lymphoproliferative response in vitro to PPD than Mantoux positive controls, indicating the presence of two populations among Eales' patients

The classical and alternate pathways of T cell activation are impaired in leprosy

The proliferative response of circulating T lymphocytes from bacterial index-positive lepromatous patients to mitogenic anti-CD3 and pairs of anti-CD2 monoclonal antibodies was significantly reduced. In these patients, the CD2 but not CD3 receptor expression was down-regulated. Further, the CD2 modulation and the associated suppression of proliferative response to monoclonals was brought about in T cells of healthy subjects by prior incubation of mononuclear cells in vitro with Mycobacterium leprae. Thus, the T cell activation pathways through the CD3 and CD2 receptors are impaired in lepromatous leprosy patients and the impairment appears to be due to the modulation of the CD2 receptor specifically by M. leprae

Immunologic unresponsiveness in leprosy is mediated by modulation of E-receptor

By using an indirect immunofluorescence technique with OKT3 and OKT11 monoclonal antibodies, the percentage of CD2 positive cells was found to be reduced in the peripheral blood of bacterial index positive lepromatous leprosy patients; however, in these patients, CD3 positive cells were at the normal level. Further, CD2 positive cells attained the normal proportion in lepromatous patients when mycobacterial load was reduced. Both CD2 and CD3 receptors were expressed at the normal level in tuberculoid leprosy patients. Prior treatment of peripheral blood mononuclear cells from healthy controls with Mycobacterium leprae significantly decreased the percentage of CD2 but not CD3 positive cells. Such a modulation of CD2 on T cells also resulted in blocking the lymphoproliferative response induced by mitogen and antigen. These results suggest that there is a strong correlation between CD2 modulation and immunologic unresponsiveness in leprosy

Priming of a β-Galactosidase (β-GAL)-Specific Type 1 Response in BALB/c Mice Infected with β-GAL-Transfected Leishmania major

To determine whether an ongoing response to Leishmania major would affect the response to a non-cross-reacting, non-leishmanial antigen, susceptible BALB/c mice and resistant C3H mice were infected with L. major parasites expressing Escherichia coli β-galactosidase (β-GAL); this parasite was designated L. major-βGAL. BALB/c and C3H mice responded to infection with L. major-βGAL by mounting a CD4 T-cell response to both parasite antigens and to the reporter antigen, β-GAL. The phenotypes of these T cells were characterized after generating T-cell lines from infected mice. As expected, BALB/c mice responded to infection with L. major-βGAL by producing interleukin 4 in response to the parasite and C3H mice produced gamma interferon (IFN-γ) in response to the parasite and β-GAL. Interestingly, however, BALB/c mice produced IFN-γ in response to β-GAL. Taken together, these results demonstrate that priming of IFN-γ-producing cells can occur in BALB/c mice despite the fact the animals are simultaneously mounting a potent Th2 response to L. major