Lymphoproliferative and cytokine responses to Cryptosporidium parvum in patients coinfected with C. parvum and human immunodeficiency virus

Abstract

We compared the lymphoproliferative and cytokine responses to Cryptosporidium parvum in human immunodeficiency virus (HIV)-seropositive and -seronegative patients. The lymphoproliferative and cytokine responses (interleukin-2 [IL-2], IL-4, IL-5, IL-10, gamma interferon, and tumor necrosis factor alpha) were assessed for 11 HIV-seropositive, Cryptosporidium-positive (group I) patients; 20 HIV-seropositive, Cryptosporidium-negative (group II) patients; 10 HIV-seronegative, Cryptosporidium-positive (group III) patients, including four post-renal transplant (group IIIa) and 6 presumably immunocompetent (group IIIb) patients; and 20 HIV-seronegative, Cryptosporidium-negative healthy individuals (group IV). No significant difference was observed in the number of patients showing positive lymphoproliferative responses in group I compared to group III (post-renal transplant [group IIIa] or immunocompetent [group IIIb]) patients, while a comparison of the median stimulation indices shows that responses were significantly lower in Cryptosporidium-infected, immunosuppressed (group I and IIIa) patients than in immunocompetent (group IIIb) patients. The number of patients showing positive responses and median stimulation indices was significantly higher for Cryptosporidium-infected (HIV-seropositive and -seronegative) individuals than for uninfected individuals, suggesting that Cryptosporidium induces significant in vitro lymphoproliferative responses in infected individuals. Cytokine levels, except for that of IL-5, were significantly higher in Cryptosporidium-infected (groups I and III) individuals than in uninfected (groups II and IV) individuals. There was no significant difference between the group I and III patients and between Cryptosporidium-infected immunosuppressed (group I or IIIa) and immunocompetent (group IIIb) patients.

FIG. 1.

Percentage of subjects with positive proliferation in response to CCA (SI > 2) and PHA (SI > 20). Gp I, group I (HIV seropositive, Cryptosporidium positive); Gp II, group II (HIV seropositive, Cryptosporidium negative); Gp III, group III (HIV seronegative, Cryptosporidium positive); Gp IIIa, group IIIa (HIV seronegative, Cryptosporidium positive, renal transplant); Gp IIIb, group IIIb (HIV seronegative, Cryptosporidium positive, immunocompetent); Gp IV, group IV (HIV seronegative, Cryptosporidium negative, healthy).

FIG. 2.

Median SI (ranges shown above the bars) following culture of PBMCs stimulated with Cryptosporidium parvum CCA and PHA. Gp I, group I (HIV seropositive, Cryptosporidium positive); Gp II, group II (HIV seropositive, Cryptosporidium negative); Gp III, group III (HIV seronegative, Cryptosporidium positive); Gp IIIa, group IIIa (HIV seronegative, Cryptosporidium positive, renal transplant); Gp IIIb, group IIIb (HIV seronegative, Cryptosporidium positive, immunocompetent); Gp IV, group IV (HIV seronegative, Cryptosporidium negative, healthy).