Yaw. Skeiky et al., IMMUNE-RESPONSES OF LEISHMANIASIS PATIENTS TO HEAT-SHOCK PROTEINS OF LEISHMANIA SPECIES AND HUMANS, Infection and immunity, 63(10), 1995, pp. 4105-4114
The course of human infection with Leishmania braziliensis is variable
, ranging from self-healing infection to chronic disease, It is theref
ore a useful system in which to study immunoregulatory aspects of leis
hmaniasis, including the effects of parasite antigens on host response
s, In the present study, we report on the cloning of, expression of, a
nd comparative analyses of patient immune response to two different L.
braziliensis genes homologous to the genes for the eukaryotic 83- and
70-kDa heat shock proteins. rLbhsp83 contains a potent T-cell epitope
(s) which stimulated peripheral blood mononuclear cells (PBMC) from al
l L. braziliensis-infected individuals to proliferate and to produce i
nterleukin-2 (IL-2) gamma interferon, and tumor necrosis factor alpha,
The elicitation of IL-4 and IL-10 mRNAs was found to differ depending
on the portion of the rLbhsp83 used to stimulate PBMC, rLbhsp83a, whi
ch represents the nearly full-length protein, stimulated IL-10 but not
IL-4 mRNA. In contrast, a similar to 43-kDa protein representing the
C-terminal region of Lbhsp83 stimulated the production of IL-4 but not
IL-10 mRNA, rLbhsp70 stimulated PBMC proliferation from patients with
mucosal disease but, unlike rLbhsp83, did not stimulate PBMC from sel
f:healing individuals, PBMC from mucosal patients were not stimulated
by rHuhsp70 to either proliferate or produce cytokines. This suggests
that the hyperresponsiveness of mucosal patient PBMC to Leishmania hea
t shock proteins does not involve an autoimmune phenomenon resulting f
rom cross-reactivity with self hsp70. In general, although the cytokin
e profile of patient PBMC in response to both of these Leishmania heat
shock proteins represents a mixed Th1-Th2 pattern, the levels of gamm
a interferon and IL-2 were significantly higher than those of the Th2
cytokines IL-4 and IL-10, Patients with active mucosal and cutaneous d
isease but not self-healing individuals had significant anti-immunoglo
bulin G antibody titers to both rLbhsp83 and rLbhsp70 but not to the h
omologous rHuhsp70. It therefore appears that differential patient imm
une responses to Leishmania hsp83 and hsp70 may be of particular signi
ficance in the induction of protective immune responses as well as in
the development of tissue damage in cases with particularly strong hyp
ersensitive reactions.