Hw. Murray et al., RESPONSE TO TREATMENT FOR AN INTRACELLULAR INFECTION IN A T-CELL-DEFICIENT HOST - TOXOPLASMOSIS IN NUDE-MICE, The Journal of infectious diseases, 167(5), 1993, pp. 1173-1177
To examine the experimental basis of treatment failures in T cell-defi
cient patients with intracellular infections, euthymic and athymic (nu
de) BALB/c mice were infected with Toxoplasma gondii and treated with
sulfadiazine. All euthymic and nude mice survived during 2 weeks of su
lfadiazine therapy. Once treatment was discontinued, 100% of euthymic
mice survived while all nude mice died. Post-sulfadiazine treatment su
rvival was enhanced in nude mice by reconstitution with either L3T4+ o
r Lyt-2+ cells and was reduced in euthymic mice by monoclonal antibody
treatment directed at depleting either L3T4+ or Lyt-2+ cells or inter
leukin-2 (IL-2) or interferon-gamma (IFN-gamma). These results suggest
that although T cells and their products are not required for an init
ial response (survival) to treatment in acute experimental toxoplasmos
is, survival off drug is strictly T cell-dependent. Optimal posttreatm
ent survival appears to involve both L3T4+ helper and Lyt-2+ cytotoxic
cells, probably acting in concert, as well as the endogenous secretio
n of at least two T cell-derived lymphokines, IL-2 and IFN-gamma.